Cytomegalovirus (CMV) is an important cause of death for patients with advanced HIV infection. CMV pneumonia is often found at autopsy, but the diagnosis is rarely established antemortem. Since effective CMV therapy is now available, early and accurate diagnosis of CMV pneumonia may be beneficial for patients. Three populations of HIV infected patients are being studied: volunteers with no pulmonary symptoms and no history of documented or empirically treated CMV disease (Group 1), volunteers with documented CMV retinitis and no pulmonary symptoms (Group 2), and patients with acute pulmonary symptoms (Group 3). Bronchoalveolar lavage (BAL) and transbronchial biopsies were performed. Specimens were assessed for the presence of CMV using microbiologic (conventional and shell vial cultures and antigen detection), cytopathologic, and histopathologic techniques. The diagnosis of CMV pneumonia required at least one typical CMV inclusion body in lung tissue and compatible pulmonary abnormalities which did not resolve with treatment for concurrent (if any) processes. Group 1 consists of 19 volunteers with a mean CD4+ lymphocyte count of 315 cells/mu L. None had histopathologic or cytopathologic evidence of CMV; however, 9/19 had CMV positive BAL cultures-none had detectable CMV antigen. Group 2 consists of 6 volunteers with a mean CD4+ lymphocyte count of 45 cells/mu L. None had histopathologic or cytopathologic evidence of CMV, however, 6/6 had CMV positive BAL cultures, yet not detectable antigen, Group 3 consists of 46 patients with a mean CD4+ lymphocyte count of 74 cells/mu L. None had histopathologic evidence of CMV; two were positive by cytopathology (CD4+ counts of O and 14 cells, respectively). CMV cultures were positive in 33/46 patients; CMV antigen was detectable in only one patient. Our preliminary conclusions are that CMV is frequently cultured from BAL of HIV infected patients, especially those with CD4+ counts less than 300 cells/mu L; serious or life-threatening pulmonary dysfunction due to CMV is rarely detectable antemortem; and CMV culture of BAL does not provide diagnostically important information and may not be cost effective. This study is larger than previously published series and answers a clinical issue using special NIH resources involving three institutes (CC,NlAID, NCI) and the FDA.